The objectives of this research are to study the demographic aspects of sickle cell anemia and related hemoglobinopathies in relationship to morbidity and mortality in the setting of comprehensive care. Psycho-social, vocational rehabilitation, specific organ defects and the effects of therapy will be documented. Specific projects will examine in detail red cell function and morphology, physiological behavior of red cells in the circulatory system and specific clinical features of the disorder. Methods to be employed include: standard and sophisticated hemoglobin electrophoresis, hemoglobin fractionation techniques, micro-manipulation of red cells including measurement of intracellular pH and cell membrane structure using magnetic resonance. Red cell rheology will be studied using in vitro techniques and circulation system costs. The effects of peroxide and specific drugs on cell function, membrane function and structure and the phenomenon of irreversible sickling will be studied using millipore filters, electron microscopy and measurement of ion flux. A service and reference laboratory will be formally established for regional consultations. Neurological studies will be conducted including EEGs, EMGs and nerve conduction, and measurement of cerebral blood flow using radio-nuclides and axial tomography. Sexual maturation, psycho-social features and results of genetic counseling will be analyzed using standard hormone measurement, psychological tests and structured behavioral change instruments.